Browsing by Subject "Center for Infectious Diseases and Microbiology Translational Research"

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    Characterizing Endothelin-1 and ABO Blood Type in Cerebral Malaria
    (2009-04-08) Ireland, Kathleen
    Malaria remains one of the most life-threatening problems in the world today. Cerebral Malaria (CM) caused by Plasmodium falciparum infection is a severe form of malarial disease that kills more than two million people annually, most of which are children. CM affects the brain and is associated with cognitive impairments, coma, and death. Left untreated, it is fatal with 24-72 hours. Quicker diagnosis is needed to provide adequate and superior treatment. In order to do so, a better understanding of the disease pathogenesis is needed. The goal of my proposed research was to further characterize endothelial cell activation in children with cerebral malaria, as well as the role of blood type as possible clinical markers that may play a role in the disease. The first aim of the project was to measure endothelin-1 levels in samples previously obtained at Mulago Hospital in Kampala, Uganda. Samples were comprised of children ages 4-12 with varying levels of disease severity. Endothelin-1 levels were measured by an immunoassay and analyzed with relation to known clinical outcomes. My second aim was to develop a polymerase chain reaction assay to determine ABO blood type from the Ugandan children's genomic DNA. I have developed a protocol using positive and negative controls that I will apply toward genotyping samples from the patients. Though this project is still in progress, I expect my results will help to characterize the role of endothelin-1 and blood type in cerebral malaria pathogenesis.
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    Fishing for Function: Identifying Functional Binding Partners of CUG-Binding Protein 1
    (2009-04-08) Jeschke, Jonathan C.
    One of the most remarkable distinguishing features of living organisms is their ability to fluidly adapt to changing environmental conditions. The advances in molecular biology over the past 50 years have resolved the general outlines this capacity for adaptation on the scale of molecules. We now view an organism’s ability to adapt as the result of many complex programs of gene expression. As a basic science, the improved resolution of these expression programs has proved invaluable in understanding many clinical pathologies, the most dramatic being cancer. My laboratory work has focused on resolving a process cells use, at the level of messenger RNA (mRNA), to turn off genes before functional proteins are made. This enzymatic process involves the break down of mRNA polymers where the degrading enzymes are recruited by specifi c adaptor proteins to specifi c sets of mRNA. One of these adaptor proteins is CUG-binding protein 1 (CUGBP1) and identifying the mRNA set CUGBP1 targets has been a focus of our lab. The degradation proteins which CUGBP1 targets to the mRNA are only poorly resolved. I am using a yeast-two hybrid screen to identify CUGBP1 binding candidates. These candidates will then be con firmed by co-immunoprecipitation and mRNA a ffinity chromatography. This will allow me to characterize the specifi c mechanism of decay elicited by the function of CUGBP1.